IMR Press / FBL / Volume 29 / Issue 2 / DOI: 10.31083/j.fbl2902052
Open Access Review
Drug Resistance in Hepatocellular Carcinoma: Theoretical Basis and Therapeutic Aspects
Ya-ruo Lei1,†Xian-lu He2,†Jun Li3,*Chun-fen Mo1,2,*
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1 Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, 610500 Chengdu, Sichuan, China
2 Department of General Surgery, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), 610083 Chengdu, Sichuan, China
3 Department of Gastroenterology, First Affiliated Hospital of Chengdu Medical College, 610500 Chengdu, Sichuan, China
*Correspondence: lijun84183967@126.com (Jun Li); mochunfen@cmc.edu.cn (Chun-fen Mo)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2024, 29(2), 52; https://doi.org/10.31083/j.fbl2902052
Submitted: 12 July 2023 | Revised: 13 October 2023 | Accepted: 21 November 2023 | Published: 4 February 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Primary liver cancer is one of the most common malignant tumors with high mortality and increasing incidence worldwide. Currently, chemotherapy is an important comprehensive treatment for moderate or advanced liver cancer. Despite the effective therapeutic effects initially achieved by chemotherapy, the high phenotypic and molecular heterogeneity of liver cancer cells facilitates resistance to conventional chemotherapy or targeted therapy and even leads to multidrug resistance (MDR), which is one of the major obstacles for clinical chemotherapy. Drug resistance exhibits multiple and complex molecular mechanisms to antagonize therapy under pharmacological pressure, including overexpression of drug efflux transporters, downstream adaptive response (such as apoptosis, autophagy, and endoplasmic reticulum stress), dysfunction of DNA damage repair (DDR), epigenetic modification, tumor microenvironment (TME) as well as extracellular matrix (ECM). In this paper, we summarize the recent research progress and intervention strategies for drug resistance in hepatocellular carcinoma (HCC), which will provide a promising therapeutic strategy for overcoming MDR in liver cancer.

Keywords
chemotherapy
hepatocellular carcinoma
multidrug resistance
tumor microenvironment
targeted therapy
immunotherapy
Funding
82170645/National Natural Science Foundation of China
2021076/Project of Chengdu Health and Family Planning Commission
2022043/Project of Chengdu Health and Family Planning Commission
24NSFSC2357/Department of Science and Technology of Sichuan Province (CN)
22NSFSC0766/Department of Science and Technology of Sichuan Province (CN)
CMC-XK-2103/Disciplinary Construction Innovation Team Foundation of Chengdu Medical College
Figures
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